title: Insertion of apoLp-III into a lipid monolayer is more favorable for saturated, more ordered, acyl-chains.
abstract: Neutral lipid transport in mammals is complicated involving many types of apolipoprotein. The exchangeable apolipoproteins mediate the transfer of hydrophobic lipids between tissues and particles, and bind to cell surface receptors. Amphipathic α-helices form a common structural motif that facilitates their lipid binding and exchangeability. ApoLp-III, the only exchangeable apolipoprotein found in insects, is a model amphipathic α-helix bundle protein and its three dimensional structure and function mimics that of the mammalian proteins apoE and apoAI. Even the intracellular exchangeable lipid droplet protein TIP47/perilipin 3 contains an α-helix bundle domain with high structural similarity to that of apoE and apoLp-III. Here, we investigated the interaction of apoLp-III from Locusta migratoria with lipid monolayers. Consistent with earlier work we find that insertion of apoLp-III into fluid lipid monolayers is highest for diacylglycerol. We observe a preference for saturated and more highly ordered lipids, suggesting a new mode of interaction for amphipathic α-helix bundles. X-ray reflectivity shows that apoLp-III unfolds at a hydrophobic interface and flexible loops connecting the amphipathic α-helices stay in solution. X-ray diffraction indicates that apoLp-III insertion into diacylglycerol monolayers induces additional ordering of saturated acyl-chains. These results thus shed important new insight into the protein-lipid interactions of a model exchangeable apolipoprotein with significant implications for its mammalian counterparts.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.
authors.forename: Sewwandi S
authors.initials: SS
authors.lastname: Rathnayake
authors.forename: Mona
authors.initials: M
authors.lastname: Mirheydari
authors.forename: Adam
authors.initials: A
authors.lastname: Schulte
authors.forename: James E
authors.initials: JE
authors.lastname: Gillahan
authors.forename: Taylor
authors.initials: T
authors.lastname: Gentit
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Rose K
authors.initials: RK
authors.lastname: Okonkwo
authors.forename: Koert N J
authors.initials: KN
authors.lastname: Burger
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Mann
authors.forename: David
authors.initials: D
authors.lastname: Vaknin
authors.forename: Wei
authors.initials: W
authors.lastname: Bu
authors.forename: Dena Mae
authors.initials: DM
authors.lastname: Agra-Kooijman
authors.forename: Edgar E
authors.initials: EE
authors.lastname: Kooijman
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D004075:Diglycerides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000737:chemistry*; D048188:Locusta migratoria / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D053838:Scattering, Small Angle; D053835:Unilamellar Liposomes / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D001053:Apolipoproteins; D004075:Diglycerides; D019476:Insect Proteins; D010743:Phospholipids; D053835:Unilamellar Liposomes
keywords: Diacylglycerol; Exchangeable apolipoprotein; Insertion isotherm; Langmuir monolayer; Protein–lipid interaction; X-ray reflectivity and diffraction